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SirA Inhibits the essential DnaA : DnaD Interaction to block helicase recruitment during Bacillus subtilis sporulation

Winterhalter, Charles; Stevens, Daniel; Fenyk, Stepan; Pelliciari, Simone; Marchand, Elie; Soultanas, Panos; Ilangovan, Aravindan; Murray, Heath


Charles Winterhalter

Daniel Stevens

Stepan Fenyk

Simone Pelliciari

Elie Marchand

Aravindan Ilangovan

Heath Murray


Bidirectional DNA replication from a chromosome origin requires the asymmetric loading of two helicases, one for each replisome. Our understanding of the molecular mechanisms underpinning helicase loading at bacterial chromosome origins is incomplete. Here we report both positive and negative mechanisms for directing helicase recruitment in the model organism Bacillus subtilis. Systematic characterization of the essential initiation protein DnaD revealed distinct protein interfaces required for homo-oligomerization, interaction with the master initiator protein DnaA, and interaction with the helicase co-loader protein DnaB. Informed by these properties of DnaD, we went on to find that the developmentally expressed repressor of DNA replication initiation, SirA, blocks the interaction between DnaD with DnaA, thereby inhibiting helicase recruitment to the origin during sporulation. These results advance our understanding of the mechanisms underpinning DNA replication initiation in B. subtilis, as well as guiding the search for essential cellular activities to target for antimicrobial drug design.


Winterhalter, C., Stevens, D., Fenyk, S., Pelliciari, S., Marchand, E., Soultanas, P., …Murray, H. (2022). SirA Inhibits the essential DnaA : DnaD Interaction to block helicase recruitment during Bacillus subtilis sporulation. Nucleic Acids Research,

Journal Article Type Article
Acceptance Date Oct 22, 2022
Online Publication Date Nov 23, 2022
Publication Date Nov 23, 2022
Deposit Date Oct 27, 2022
Publicly Available Date Nov 23, 2022
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Keywords Chromosome, DnaD, DnaA, SirA, helicase, origin, replication
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